Project description
The role of polyunsaturated fatty acids in gut inflammation
Inflammatory bowel diseases (IBDs) such as ulcerative colitis and Crohn’s disease are characterised by chronic inflammation in the gut. Even though genetic factors contribute to the pathogenesis of IBDs, environmental triggers such as diet are thought to shape the course of the disease. The EU-funded MEGI CD project focuses on the role of polyunsaturated fatty acids (PUFAs) in gut inflammation. PUFAs include omega-3 and omega-6 fats, which are considered to be healthy and part of a balanced diet. Researchers will employ in vitro and preclinical models of IBDs to study the mechanism by which dietary PUFAs can elicit gut inflammation and further exacerbate disease.
Objective
The rising incidence of inflammatory bowel diseases such as Crohn?s disease (CD) has become a global health care issue in the 21st century. The complex genetic underpinning is increasingly appreciated, while environmental cues and specifically a Western diet are suspected to impact development and course of disease. Mechanistic insights that would support this assumption remain scarce and specific nutrients that trigger a flare are unknown. Westernisation of dietary habits is partly characterised by enrichment of long-chain fatty acids, which fuel metabolic inflammation of tissues beyond the gut. Here, we propose to establish the concept of metabolic gut inflammation as a fuel for CD. By analysing transgenic mice, human CD organoids and two independent CD patient cohorts, we seek to establish how dietary polyunsaturated fatty acids (PUFAs) affect gut inflammation and disease course. The proposed work is based on our previous observations that dietary PUFAs trigger a chemokine response and Crohn?s-like enteritis in mice, which is restricted by intestinal epithelial Glutathione peroxidase 4 (GPX4). GPX4 is an evolutionary conserved anti-oxidative enzyme which shows impaired activity in CD epithelium. The proposed work will identify how dietary PUFAs elicit gut inflammation in mice and which epithelial lineage executes the inflammatory response. In a next step, I propose to establish a critical crosstalk between GPX4 and metabolic hubs in gut epithelium to provide a basis for the concept of metabolic gut inflammation. Finally, we seek to translate findings by establishing that PUFAs evoke an inflammatory response from CD epithelium, and that PUFA intake impacts disease course. MEGI CD comprehends basic and translational science to set the basis for novel therapeutic strategies in a complex illness that requires better treatment modalities. The study will prove the concept of metabolic gut inflammation as a major driver of human CD, a basis for nutritional therapy.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been validated by the project's team.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
This project's classification has been validated by the project's team.
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2021-STG
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6020 INNSBRUCK
Austria
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